Amino Acids
· 2024 Feb · PMID 38358574
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Antimicrobial peptide (AMP) is the polypeptide, which protects the organism avoiding attack from pathogenic bacteria. Studies have shown that there were some antimicrobial peptides with molecular action mechanism involve...Antimicrobial peptide (AMP) is the polypeptide, which protects the organism avoiding attack from pathogenic bacteria. Studies have shown that there were some antimicrobial peptides with molecular action mechanism involved in crossing the cell membrane without inducing severe membrane collapse, then interacting with cytoplasmic target-nucleic acid, and exerting antibacterial activity by interfacing the transmission of genetic information of pathogenic microorganisms. However, the relationship between the antibacterial activities and peptide structures was still unclear. Therefore, in the present work, a series of AMPs with a sequence of 20 amino acids was extracted from DBAASP database, then, quantitative structure-activity relationship (QSAR) methods were conducted on these peptides. In addition, novel antimicrobial peptides with stronger antimicrobial activities were designed according to the information originated from the constructed models. Hence, the outcome of this study would lay a solid foundation for the in-silico design and exploration of novel antibacterial peptides with improved activity activities.
Han X, Chen L, Sun P
… +6 more, Wang X, Zhao Q, Liao L, Lou D, Zhou N, Wang Y
Amino Acids
· 2024 Feb · PMID 38351332
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The advance of high-throughput sequencing enhances the discovery of short ORFs embedded in long non-coding RNAs (lncRNAs). Here, we uncovered the production and biological activity of lncRNA-hidden polypeptides in lung a...The advance of high-throughput sequencing enhances the discovery of short ORFs embedded in long non-coding RNAs (lncRNAs). Here, we uncovered the production and biological activity of lncRNA-hidden polypeptides in lung adenocarcinoma (LUAD). In the present study, bioinformatics was used to screen the lncRNA-hidden polypeptides in LUAD. Analysis of protein expression was done by western blot or immunofluorescence assay. The functions of the polypeptide were determined by detecting its effects on cell viability, proliferation, migration, invasion, and pemetrexed (PEM) sensitivity. The protein interactors of the polypeptide were analyzed by mass spectrometry after Co-immunoprecipitation (Co-IP) assay. The results showed that the lncRNA LINC00954 was confirmed to encode a novel polypeptide LINC00954-ORF. The polypeptide had tumor-suppressor features in A549 cells by repressing cell growth, motility and invasion. Moreover, the polypeptide enhanced PEM sensitivity and suppressed growth in A549/PEM cells. The protein interactors of this polypeptide had close correlations with RNA processing, amide metabolic process, translation, RNA binding, RNA transport, and DNA replication. As a conclusion, the LINC00954-ORF polypeptide embedded in lncRNA LINC00954 possesses tumor-suppressor features in A549 and PEM-resistant A549 cells and sensitizes PEM-resistant A549 cells to PEM, providing evidence that the LINC00954-ORF polypeptide is a potential anti-cancer agent in LUAD.
Kamada N, Ikeda A, Makino Y
… +1 more, Matsubara H
Amino Acids
· 2024 Feb · PMID 38340233
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Glycogen phosphorylase (GP) is biologically active as a dimer of identical subunits, each activated by phosphorylation of the serine-14 residue. GP exists in three interconvertible forms, namely GPa (di-phosphorylated fo...Glycogen phosphorylase (GP) is biologically active as a dimer of identical subunits, each activated by phosphorylation of the serine-14 residue. GP exists in three interconvertible forms, namely GPa (di-phosphorylated form), GPab (mono-phosphorylated form), and GPb (non-phosphorylated form); however, information on GPab remains scarce. Given the prevailing view that the two GP subunits collaboratively determine their catalytic characteristics, it is essential to conduct GPab characterization to gain a comprehensive understanding of glycogenolysis regulation. Thus, in the present study, we prepared rabbit muscle GPab from GPb, using phosphorylase kinase as the catalyst, and identified it using a nonradioactive phosphate-affinity gel electrophoresis method. Compared with the half-half GPa/GPb mixture, the as-prepared GPab showed a unique AMP-binding affinity. To further investigate the intersubunit communication in GP, its catalytic site was probed using pyridylaminated-maltohexaose (a maltooligosaccharide-based substrate comprising the essential dextrin structure for GP; abbreviated as PA-0) and a series of specifically modified PA-0 derivatives (substrate analogs lacking part of the essential dextrin structure). By comparing the initial reaction rates toward the PA-0 derivative (V) and PA-0 (V), we demonstrated that the V/V ratio for GPab was significantly different from that for the half-half GPa/GPb mixture. This result indicates that the interaction between the two GP subunits significantly influences substrate recognition at the catalytic sites, thereby providing GPab its unique substrate recognition profile.
Valipour H, Meftahi GH, Pirzad Jahromi G
… +1 more, Mohammadi A
Amino Acids
· 2024 Feb · PMID 38340185
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Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT receptor) lateralization in the b...Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT receptor) lateralization in the basolateral amygdala (BLA) in vivo on anxiety and metabolic behaviors under stress. In the present study, the effect of unilateral and bilateral suppression of the 5-HT receptor in the BLA on anxiety, and metabolic responses to chronic restraint stress was assessed. Male Wistar rats 7 days after cannulation into the BLA received chronic restraint stress for 14 consecutive days. 20 minutes before induction of stress, WAY-100-635 (selective 5-HT antagonist) or sterile saline (vehicle) was administered either uni- or bi-laterally into the BLA. Behavioral (elevated plus maze; EPM, and open field test), and metabolic parameter studies were performed. Results showed that stress causes a significant increase in weight gain compared to control. In the non-stress condition, the left and bilaterally, and in the stress condition the right, left, and both sides, inhibition of 5-HT in the BLA reduced weight gain. In the restraint stress condition, only inhibition of the 5-HT receptor in the left BLA led to decreased food intake compared to the control group. In stress conditions, inhibition of the 5-HT receptor on the right, left, and bilateral BLA increased water intake compared to the stress group. Inhibition of the 5-HT receptor on the left side of the BLA by WAY-100-635 induced anxiety-like behaviors in stressed rats. Similarly, WAY-100-635 on the left BLA effectively caused anxiety-like behaviors in both EPM and open field tests in the control animals. In conclusion, it seems that 5-HT receptors in the left BLA are more responsible for anxiety-like behaviors and metabolic changes in responses to stress.
Antony A, Purayil AK, Olakkaran S
… +4 more, Dhannura S, Shekh S, Gowd KH, Gurushankara HP
Amino Acids
· 2024 Feb · PMID 38319435
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Temporin-SHf is a linear, ultra-short, hydrophobic, α-helix, and phe-rich cationic antimicrobial peptide. The antitumor activities and mechanism of temporin-SHf-induced cancer cell death are unknown. The temporin-SHf was...Temporin-SHf is a linear, ultra-short, hydrophobic, α-helix, and phe-rich cationic antimicrobial peptide. The antitumor activities and mechanism of temporin-SHf-induced cancer cell death are unknown. The temporin-SHf was synthesized by solid-phase Fmoc chemistry and antimicrobial and antitumor activities were investigated. Temporin-SHf was microbiocidal, non-hemolytic, and cytotoxic to human cancer cells but not to non-tumorigenic cells. It affected the cancer cells' lysosomal integrity and caused cell membrane damage. The temporin-SHf inhibited A549 cancer cell proliferation and migration. It is anti-angiogenic and causes cancer cell death through apoptosis. The molecular mechanism of action of temporin-SHf confirmed that it kills cancer cells by triggering caspase-dependent apoptosis through an intrinsic mitochondrial pathway. Owing to its short length and broad spectrum of antitumor activity, temporin-SHf is a promising candidate for developing a new class of anticancer drugs.
Jin YW, Ma YR, Zhang MK
… +5 more, Xia WB, Yuan P, Li BX, Wei YH, Wu XA
Amino Acids
· 2024 Feb · PMID 38319413
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The organic anion-transporting polypeptide 1B3 and P-glycoprotein (P-gp) provide efficient directional transport (OATP1B3-P-gp) from the blood to the bile that serves as a key determinant of hepatic disposition of the dr...The organic anion-transporting polypeptide 1B3 and P-glycoprotein (P-gp) provide efficient directional transport (OATP1B3-P-gp) from the blood to the bile that serves as a key determinant of hepatic disposition of the drug. Unfortunately, there is still a lack of effective means to evaluate the disposal ability mediated by transporters. The present study was designed to identify a suitable endogenous biomarker for the assessment of OATP1B3-P-gp function in the liver. We established stably transfected HEK293T-OATP1B3 and HEK293T-P-gp cell lines. Results showed that azelaic acid (AzA) was an endogenous substrate for OATP1B3 and P-gp using serum pharmacology combined with metabolomics. There is a good correlation between the serum concentration of AzA and probe drugs of rOATP1B3 and rP-gp when rats were treated with their inhibitors. Importantly, after 5-fluorouracil-induced rat liver injury, the relative mRNA level and expression of rOATP1B3 and rP-gp were markedly down-regulated in the liver, and the serum concentration of AzA was significantly increased. These observations suggest that AzA is an endogenous substrate of both OATP1B3 and P-gp, and may serve as a potential endogenous biomarker for the assessment of the function of OATP1B3-P-gp for the prediction of changes in the pharmacokinetics of drugs transported by OATP1B3-P-gp in liver disease states.
Pinckaers PJM, Weijzen MEG, Houben LHP
… +6 more, Zorenc AH, Kouw IWK, de Groot LCPGM, Verdijk LB, Snijders T, van Loon LJC
Amino Acids
· 2024 Feb · PMID 38315260
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Plant-derived proteins are generally believed to possess lesser anabolic properties when compared with animal-derived proteins. This is, at least partly, attributed to the lower leucine content of most plant-derived prot...Plant-derived proteins are generally believed to possess lesser anabolic properties when compared with animal-derived proteins. This is, at least partly, attributed to the lower leucine content of most plant-derived proteins. Corn protein has a leucine content that is highest among most plant-derived proteins and it even exceeds the levels observed in animal-derived proteins such as whey protein. Therefore, this study aimed to compare muscle protein synthesis rates following the ingestion of 30 g corn protein and a 30 g blend of corn plus milk protein with 30 g milk protein. In a randomized, double blind, parallel-group design, 36 healthy young males (26 ± 4 y) received primed continuous L-[ring-C]-phenylalanine infusions and ingested 30 g corn protein (CORN), 30 g milk protein (MILK), or a 30 g proteinblend with 15 g corn plus 15 g milk protein (CORN + MILK). Blood and muscle biopsies were collected for 5 h following protein ingestion to assess post-prandial plasma amino acid profiles and myofibrillar protein synthesis rates. The results show that Ingestion of protein increased myofibrillar protein synthesis rates from basal post-absorptive values in all treatments(P < 0.001). Post-prandial myofibrillar protein synthesis rates did not differ between CORN vs MILK (0.053 ± 0.013 vs 0.053 ± 0.013%∙h, respectively; t-test P = 0.90), or between CORN + MILK vs MILK (0.052 ± 0.024 vs 0.053 ± 0.013%∙h, respectively; t-test P = 0.92). Ingestion of 30 g corn protein, 30 g milk protein, or a blend of 15 g corn plus 15 g milk protein robustly increases muscle protein synthesis rates in young males. The muscle protein synthetic response to the ingestion of 30 g corn-derived protein does not differ from the ingestion of an equivalent amount of milk protein in healthy, young males. Clinical Trial Registry number. NTR6548 (registration date: 27-06-2017) https://www.trialregister.nl/ .
Zhuang H, Cao X, Tang X
… +7 more, Zou Y, Yang H, Liang Z, Yan X, Chen X, Feng X, Shen L
Amino Acids
· 2024 Feb · PMID 38315232
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Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that lacks convenient and accessible peripheral blood diagnostic markers and effective drugs. Metabolic dysfunction is one of AD risk factors, which...Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that lacks convenient and accessible peripheral blood diagnostic markers and effective drugs. Metabolic dysfunction is one of AD risk factors, which leaded to alterations of various metabolites in the body. Pathological changes of the brain can be reflected in blood metabolites that are expected to explain the disease mechanisms or be candidate biomarkers. The aim of this study was to investigate the changes of targeted metabolites within peripheral blood of AD mouse model, with the purpose of exploring the disease mechanism and potential biomarkers. Targeted metabolomics was used to quantify 256 metabolites in serum of triple transgenic AD (3 × Tg-AD) male mice. Compared with controls, 49 differential metabolites represented dysregulation in purine, pyrimidine, tryptophan, cysteine and methionine and glycerophospholipid metabolism. Among them, adenosine, serotonin, N-acetyl-5-hydroxytryptamine, and acetylcholine play a key role in regulating neural transmitter network. The alteration of S-adenosine-L-homocysteine, S-adenosine-L-methionine, and trimethylamine-N-oxide in AD mice serum can served as indicator of AD risk. The results revealed the changes of metabolites in serum, suggesting that metabolic dysregulation in periphery in AD mice may be related to the disturbances in neuroinhibition, the serotonergic system, sleep function, the cholinergic system, and the gut microbiota. This study provides novel insights into the dysregulation of several key metabolites and metabolic pathways in AD, presenting potential avenues for future research and the development of peripheral biomarkers.
Amino Acids
· 2024 Feb · PMID 38315214
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Nanostructures formed by the self-assembly of modified/unmodified amino acids have the potential to be useful in several biological/nonbiological applications. In that regard, the greater conformational space provided by...Nanostructures formed by the self-assembly of modified/unmodified amino acids have the potential to be useful in several biological/nonbiological applications. In that regard, the greater conformational space provided by γ-amino acids, owing to their additional backbone torsional degrees of freedom and enhanced proteolytic stability, compared to their α-counterparts, should be explored. Though, modified single amino acid-based nanomaterials such as nanobelts or hydrogels are developed by utilizing the monosubstituted γ-amino acids derived from the backbone homologation of phenylalanine (Phe). Examples of a single γ-amino acid-based porous nanostructure capable of accommodating solvent molecules are not really known. The crystal structures of a modified γ(R)Phe residue, Boc-γ(R)Phe-OH, at different temperatures, showed that hydrogen-bonded water molecules are forming a wire inside hydrophilic nanochannels. The dynamics of intermolecular interactions between the water wire and the inner wall of the channel with relation to the temperature change was investigated by analyzing the natural bonding orbital (NBO) calculation results performed with the single crystal structures obtained at different temperature points. The NBO results showed that from 325 K onward, the strength of water-water interactions in the water wire are getting weaker, whereas, for the water-inner wall interactions, it getting stronger, suggesting a favorable change in the orientation of water molecules with temperatures, for the latter.
Amino Acids
· 2024 Feb · PMID 38310598
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As a catabolic process, autophagy through lysosomes degrades defective and damaged cellular materials to support homeostasis in stressful conditions. Therefore, autophagy dysregulation is associated with the induction of...As a catabolic process, autophagy through lysosomes degrades defective and damaged cellular materials to support homeostasis in stressful conditions. Therefore, autophagy dysregulation is associated with the induction of several human pathologies, including cancer. Although the role of autophagy in cancer progression has been extensively studied, many issues need to be addressed. The available evidence suggest that autophagy shows both cytoprotective and cytotoxic mechanisms. This dual role of autophagy in cancer has supplied a renewed interest in the development of novel and effective cancer therapies. Considering this, a deeper understanding of the molecular mechanisms of autophagy in cancer treatment is crucial. This article provides a summary of the recent advances regarding the dual and different mechanisms of autophagy-mediated therapeutic efficacy in cancer.
Yap SH, Lee CS, Zulkifli ND
… +5 more, Suresh D, Hamase K, Das KT, Rajasuriar R, Leong KH
Amino Acids
· 2024 Feb · PMID 38310167
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Studies in vivo have demonstrated that the accumulation of D-amino acids (D-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not...Studies in vivo have demonstrated that the accumulation of D-amino acids (D-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of D-AAs by D-amino oxidase (DAO) produces hydrogen peroxide (HO), a reactive oxygen species involved in several physiological processes including immune response, cell differentiation, and proliferation. Excessive levels of HO contribute to oxidative stress and eventual cell death, a characteristic of age-related pathology. Here, we explored the molecular mechanisms of D-serine (D-Ser) and D-alanine (D-Ala) in human liver cancer cells, HepG2, with a focus on the production of HO the downstream secretion of pro-inflammatory cytokine and chemokine, and subsequent cell death. In HepG2 cells, we demonstrated that D-Ser decreased HO production and induced concentration-dependent depolarization of mitochondrial membrane potential (MMP). This was associated with the upregulation of activated NF-кB, pro-inflammatory cytokine, TNF-α, and chemokine, IL-8 secretion, and subsequent apoptosis. Conversely, D-Ala-treated cells induced HO production, and were also accompanied by the upregulation of activated NF-кB, TNF-α, and IL-8, but did not cause significant apoptosis. The present study confirms the role of both D-Ser and D-Ala in inducing inflammatory responses, but each via unique activation pathways. This response was associated with apoptotic cell death only with D-Ser. Further research is required to gain a better understanding of the mechanisms underlying D-AA-induced inflammation and its downstream consequences, especially in the context of aging given the wide detection of these entities in systemic circulation.
Borges N, Doering TM, Murphy G
… +2 more, Macdonald M, Dunstan RH
Amino Acids
· 2024 Feb · PMID 38300362
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This study investigated the effect of high-intensity interval exercise on total and individual amino acid concentrations in red blood cells (RBCs) and plasma. Seven males (31 ± 13 yr) provided venous blood samples at res...This study investigated the effect of high-intensity interval exercise on total and individual amino acid concentrations in red blood cells (RBCs) and plasma. Seven males (31 ± 13 yr) provided venous blood samples at rest, immediately and 15 min and 30 min following an 8-min high-intensity exercise bout. The exercise bout was 16 × 15 s cycle efforts at 0.4N/kg of body mass and 90 rpm, interspersed with 15 s passive recovery. Total and individual amino acid concentrations of RBC and plasma and blood cell parameters were analysed. No significant differences for total amino acid concentrations between RBC and plasma were found. Individual amino acid analyses showed significant interaction effects for alanine and α-aminoadipic acid (P < 0.05), with plasma alanine significantly increased from baseline across the recovery period (P < 0.001). Blood fraction (group) effects showed greater concentrations of glycine, serine, asparagine, aspartic acid, glutamic acid, α-aminoadipic acid and ornithine in RBC, while greater concentrations of alanine, α-aminobutyric acid, valine, leucine, isoleucine, threonine, proline, phenylalanine, glutamine, tryptophan and cystine were found in plasma (P < 0.05). Comparable levels of histidine, lysine and tyrosine were observed between blood fractions. Significant differences in the variation of total amino acids in RBC were reported with higher variance at rest compared to following exercise (P = 0.01). Haemoglobin, pack cell volume and white blood cell count significantly increased immediately following exercise (P < 0.05) but returned to baseline after 15 min recovery. These results support the notion of individualised amino acid transportation roles for RBC and plasma during exercise.
Amino Acids
· 2024 Feb · PMID 38300332
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Four linear amino acids of increased separation of the carboxyl and amino groups, namely glycine (aminoacetic acid), β-alanine (3-aminopropanoic acid), GABA (4-aminobutanoic acid) and DAVA (5-aminopentanoic acid), have b...Four linear amino acids of increased separation of the carboxyl and amino groups, namely glycine (aminoacetic acid), β-alanine (3-aminopropanoic acid), GABA (4-aminobutanoic acid) and DAVA (5-aminopentanoic acid), have been studied by quantum chemical ab initio and DFT methods including the solvent effect in order to get electronic structure and molecular descriptors, such as ionisation energy, electron affinity, molecular electronegativity, chemical hardness, electrophilicity index, dipole moment, quadrupole moment and dipole polarizability. Thermodynamic functions (zero-point energy, inner energy, enthalpy, entropy, and the Gibbs energy) were evaluated after the complete vibrational analysis at the true energy minimum provided by the full geometry optimization. Reaction Gibbs energy allows evaluating the absolute redox potentials on reduction and/or oxidation. The non-local non-additive molecular descriptors were compared along the series showing which of them behave as extensive, varying in match with the molar mass and/or separation of the carboxyl and amino groups. Amino acidic forms and zwitterionic forms of the substances were studied in parallel in order to compare their relative stability and redox properties. In total, 24 species were investigated by B3LYP/def2-TZVPD method (M1) including neutral molecules, molecular cations and molecular anions. For comparison, MP2/def2-TZVPD method (M2) with full geometry optimization and vibrational analysis in water has been applied for 12 species; analogously, for 24 substances, DLPNO-CCSD(T)/aug-cc-pVTZ method (M3) has been applied in the geometry obtained by MP2 and/or B3LYP. It was found that the absolute oxidation potential correlates with the adiabatic ionisation energy; the absolute reduction potential correlates with the adiabatic electron affinity and the electrophilicity index. In order to validate the used methodology with experimental vertical ionisation energies and vibrational spectrum obtained in gas phase, calculations were done also in vacuo.
de Bastos Balbe E Gutierres M, Pedebos C, Bacaicoa-Caruso P
… +1 more, Ligabue-Braun R
Amino Acids
· 2024 Jan · PMID 38286913
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Viral diseases are expected to cause new epidemics in the future, therefore, it is essential to assess how viral diversity is represented in terms of deposited protein structures. Here, data were collected from the Prote...Viral diseases are expected to cause new epidemics in the future, therefore, it is essential to assess how viral diversity is represented in terms of deposited protein structures. Here, data were collected from the Protein Data Bank to screen the available structures of viruses of interest to WHO. Excluding SARS-CoV-2 and HIV-1, less than 50 structures were found per year, indicating a lack of diversity. Efforts to determine viral structures are needed to increase preparedness for future public health challenges.
Mzedawee HRH, Kowsar R, Moradi-Hajidavaloo R
… +4 more, Shiasi-Sardoabi R, Sadeghi K, Nasr-Esfahani MH, Hajian M
Amino Acids
· 2024 Jan · PMID 38285159
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By affecting the ovarian pool of follicles and their enclosed oocytes, heat stress has an impact on dairy cow fertility. This study aimed to determine how heat shock (HS) during in vitro maturation affected the ability o...By affecting the ovarian pool of follicles and their enclosed oocytes, heat stress has an impact on dairy cow fertility. This study aimed to determine how heat shock (HS) during in vitro maturation affected the ability of the bovine cumulus-oocyte complexes (COCs) to develop, as well as their metabolism of amino acids (AAs). In this study, COCs were in vitro matured for 23 h at 38.5 °C (control; n = 322), 39.5 °C (mild HS (MHS); n = 290), or 40.5 °C (severe HS (SHS); n = 245). In comparison to the control group, the MHS and SHS groups significantly decreased the percentage of metaphase-II oocytes, as well as cumulus cell expansion and viability. The SHS decreased the rates of cleavage and blastocyst formation in comparison to the control and MHS. Compared to the control and MHS-COCs, the SHS-COCs produced significantly more phenylalanine, threonine, valine, arginine, alanine, glutamic acid, and citrulline while depleting less leucine, glutamine, and serine. Data showed that SHS-COCs had the highest appearance and turnover of all AAs and essential AAs. Heat shock was positively correlated with the appearance of glutamic acid, glutamine, isoleucine, alanine, serine, valine, phenylalanine, and asparagine. Network analysis identified the relationship between HS and alanine or glutamic acid, as well as the relationship between blastocyst and cleavage rates and ornithine. The findings imply that SHS may have an impact on the quality and metabolism of AAs in COCs. Moreover, the use of a multistep analysis could simply identify the AAs most closely linked to HS and the developmental competence of bovine COCs.
Mendonça FF, Sobral DV, Durante ACR
… +7 more, Miranda ACC, Mejia J, de Paula Faria D, Marques FLN, de Barboza MF, Fuscaldi LL, Malavolta L
Amino Acids
· 2024 Jan · PMID 38285098
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Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequenc...Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, β1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [I]I-YIKVAV and [I]I-YIGSR. Conversely, [I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [I]I-YIKVAV and [I]I-YIGSR reached ≅ 48% and ≅ 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and β1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.
The conjugation of active biomolecules provides insight into their bioreactivity, leading to many applications in biotechnology and materials science. Herein, we report L-selenocystine (SeC) bioconjugates of lipoic acid...The conjugation of active biomolecules provides insight into their bioreactivity, leading to many applications in biotechnology and materials science. Herein, we report L-selenocystine (SeC) bioconjugates of lipoic acid (universal antioxidant) and biotin (Vitamin-H). The SeC-bioconjugates, SeC-Biotin (1) and SeC-Lipoic acid (2) were synthesized using solid phase peptide synthesis (SPPS) method and were characterized by multinuclear 1D (H, C, Se) and 2D (H-H COSY and H-C TOCSY) NMR spectroscopy, ESI-MS spectrometry, and RP-HPLC. The GPx-like enzyme mimicking activity of the SeC-bioconjugates 1 and 2 has been investigated through the coupled reductase assay method for the catalytic reductions of hydrogen peroxide into water A significant enhancement in GPx-like enzymatic activity was observed for both novel bioconjugates SeC-Biotin (1) and SeC-Lipoic acid (2) as compared to diphenyl diselenide (PhSe), L-selenocystine (SeC), biotin, lipoic acid, and ebselen.